Essential Role of Voltage-Dependent Anion Channel in Various Forms of Apoptosis in Mammalian Cells

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  • Shigeomi Shimizu
    aOsaka University Graduate School of Medicine, Biomedical Research Center, Department of Medical Genetics, Osaka 565-0871, Japan
  • Yosuke Matsuoka
    bDepartment of Cell Biology and Neuroscience, Osaka 565-0871, Japan
  • Yasuo Shinohara
    dUniversity of Tokushima, Faculty of Pharmaceutical Sciences, Tokushima 770-8505, Japan
  • Yoshihiro Yoneda
    bDepartment of Cell Biology and Neuroscience, Osaka 565-0871, Japan
  • Yoshihide Tsujimoto
    aOsaka University Graduate School of Medicine, Biomedical Research Center, Department of Medical Genetics, Osaka 565-0871, Japan

書誌事項

公開日
2001-01-22
DOI
  • 10.1083/jcb.152.2.237
公開者
Rockefeller University Press

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<jats:p>Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Δψ), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.</jats:p>

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